Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology
Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology
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DOI：
10.1016/j.nicl.2020.102369
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发表时间：
2020-01-01
影响因子：
4.2
通讯作者：
Gorno-Tempini, M. L.
中科院分区：
文献类型：
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作者：
Borghesani, V.;Battistella, G.;Gorno-Tempini, M. L.
尸检研究表明，局灶性颞叶前部（ATL）神经退行性变最常由额颞叶变性TDP - 43 C型病理引起。临床上，根据主要症状是否影响语言、物体或人物的语义知识或社会情感行为，这些患者被用不同的术语描述，例如语义变异型原发性进行性失语（svPPA）、语义性痴呆（SD）或右侧颞叶变异型额颞叶痴呆（FTD）。ATL萎缩呈现不同程度的偏侧化，右侧病例被认为较为罕见，尽管由于对特征明确、经病理证实的队列研究较少，其患病率的估计受到阻碍。此外，尚不清楚左右侧变异在ATL内横断面上和纵向上是否显示出相似的萎缩分布。在此，我们研究了迄今为止最大的经病理证实的在生前被诊断为svPPA、SD或右侧颞叶变异型FTD的TDP - 43 - C病例队列。我们分析了30例病例的临床、认知和神经影像学数据，其中一部分进行了纵向随访。在近期结构和功能分区研究的指导下，我们构建了四个双侧ATL感兴趣区域（ROIs）。通过计算萎缩偏侧化指数，可以比较两个半球之间的萎缩模式。这导致了基于影像学的病例自动分类为左侧优势型或右侧优势型。然后我们比较了两组在ATL感兴趣区域内的区域萎缩模式（横断面）和萎缩进展（纵向）。结果显示，经病理证实的被诊断为颞叶变异型的TDP - 43 - C病例中有40%呈现右侧偏侧化萎缩。此外，我们的ATL感兴趣区域分析结果表明，无论萎缩偏侧化如何，两个ATL内的萎缩分布都遵循从内侧到外侧的梯度。最后，在左右侧病例中，萎缩似乎都进展到对侧ATL，并从前颞极发展到后颞叶和眶额叶区域。综上所述，我们的研究结果表明，在TDP - 43 - C病理中，初期右侧优势型ATL萎缩很常见，并且左右侧变异在ATL内的损伤分布似乎相同。因此，无论临床表型和萎缩偏侧化有何差异，FTD的两种颞叶变异都应被视为同一疾病的谱系表现。
Post-mortem studies show that focal anterior temporal lobe (ATL) neurodegeneration is most often caused by frontotemporal lobar degeneration TDP-43 type C pathology. Clinically, these patients are described with different terms, such as semantic variant primary progressive aphasia (svPPA), semantic dementia (SD), or right temporal variant frontotemporal dementia (FTD) depending on whether the predominant symptoms affect language, semantic knowledge for object or people, or socio-emotional behaviors. ATL atrophy presents with various degrees of lateralization, with right-sided cases considered rarer even though estimation of their prevalence is hampered by the paucity of studies on well-characterized, pathology-proven cohorts. Moreover, it is not clear whether left and right variants show a similar distribution of atrophy within the ATL cross-sectionally and longitudinally.Here we study the largest cohort to-date of pathology-proven TDP-43-C cases diagnosed during life as svPPA, SD or right temporal variant FTD. We analyzed clinical, cognitive, and neuroimaging data from 30 cases, a subset of which was followed longitudinally. Guided by recent structural and functional parcellation studies, we constructed four bilateral ATL regions of interest (ROIs). The computation of an atrophy lateralization index allowed the comparison of atrophy patterns between the two hemispheres. This led to an automatic, imaging-based classification of the cases as left-predominant or right-predominant. We then compared the two groups in terms of regional atrophy patterns within the ATL ROIs (cross-sectionally) and atrophy progression (longitudinally).Results showed that 40% of pathology proven cases of TDP-43-C diagnosed with a temporal variant presented with right-lateralized atrophy. Moreover, the findings of our ATL ROI analysis indicated that, irrespective of atrophy lateralization, atrophy distribution within both ATLs follows a medial-to-lateral gradient. Finally, in both left and right cases, atrophy appeared to progress to the contralateral ATL, and from the anterior temporal pole to posterior temporal and orbitofrontal regions.Taken together, our findings indicate that incipient right predominant ATL atrophy is common in TDP-43-C pathology, and that distribution of damage within the ATLs appears to be the same in left- and right- sided variants. Thus, regardless of differences in clinical phenotype and atrophy lateralization, both temporal variants of FTD should be viewed as a spectrum presentation of the same disease.